The long term objective of this proposal is the investigation with noninvasive techniques of the physiology of the retinal, optic nerve head and choroidal circulation and the role played by these circulations in the development of ocular fundus diseases. In the period of this grant, we will: a) develop laser Doppler velocimetry (LDV) methods to measure velocity, volume and flow of blood in the optic nerve head and choroidal circulations that are applicable in human subjects; b)investigate the physiology of these circulations, specifically the blood flow regulation in response to various physiological stresses such as hyperoxia, hypercapnia and moderate changes in ocular perfusion pressure; c) investigate the regulation of peripheral and macular retinal blood flow (RBF) in response to changes in fundus illumination; d) investigate retinal hemodynamics in early diabetes mellitus to determine whether it is abnormal in diabetic patients without retinopathy; e) investigate whether diabetic eyes with or without each of the following: serve capillary non perfusion, NVD, NVE and vitreous hemorrhage have RBF and RBF response to hyperoxia are different; f) investigate the potential of infrared LDV to localize neovascular membranes in age related macular degeneration. It is expected that these studies will increase our understanding of the ocular fundus circulation and of the microvascular pathophysiology in diabetic retinopathy. The development of noninvasive techniques to measure optic nerve and choroidal circulation may ultimately help substantiate or dismiss the vasogenic theory of glaucoma.